We will describe the nature and extent of the marked serotypic diversity of Rickettsia tsutsugamushi, the causative agent of scrub typhus, in terms of molecular protein structure. We will examine the diversity of polypeptide patterns among R. tsutsugamushi isolates, and assign them to subgroups according to total protein profiles (by polyacrylamide gel electrophoresis (SDS-PAGE)) and the serologic specificity of individual protein antigens (by SDS-PAGE of immunoprecipitated proteins). Some physical characteristics of outer membrane proteins (particularly antigens) will be described. Preliminary studies have shown that (1) established scrub typhus strains can be distinguished by SDS-PAGE polypeptide profiles, (2) isolates classified as belonging to the same serotype by standard techniques nevertheless can be differentiated by our new methods, and (3) a number of rickettsial proteins can be identified as antigens by immunoprecipitation coupled with SDS-PAGE. The analysis of R. tsutsugamushi proteins and outer membrane protein antigens will provide the basis for determining (1) the geographic range of individual R. tsutsugamushi strains, (2) their stability in the face of selective pressures, (3) the role that surface proteins play in functions critical to rickettsial virulence, and (4) which antigens might be used for immunoprophylaxis or serodiagnosis of scrub typhus in humans.